Anti-N-Methyl-D-Aspartate receptor encephalitis

Nervous system paraneoplastic syndromes 

Also known as anti-NMDA encephalitis.
This is a type of encephalitis.

 

Investigations 

• Anti-NMDA receptor antibodies

VIPoma

This is a type of pancreatic cancer called a pancreatic neuroendocrine tumour (PNET).
These originate in the pancreatic islets.

Zollinger-Ellison syndrome

Disease class: Intestinal diseases

Disease class: Paraneoplastic endocrine syndromes

Disease class: Stomach diseases

Also known as pancreatic ulcerogenic tumor syndrome.

Caused by a gastrin secreting gastrinoma.

Complications

• Gasto-oesophageal reflux disease
• Peptic ulcer disease

Parathyroid adenoma

This is a neoplasm of the parathyroid glands.
There is usually excessive production of parathyroid hormone (PTH) resulting in hyperparathyroidism. 

Gastrinoma

This is a type of pancreatic cancer called a pancreatic neuroendocrine tumour (PNET).
These originate in the pancreatic islets.


Gastrinoma refers to a gastrin secreting neoplasm.
It causes pancreatic ulcerogenic tumor syndrome, also known as Zollinger-Ellison syndrome.

Inappropriate ADH Syndrome

Disease class: Pituitary diseases
Disease class: Water-electrolyte imbalance

Hormones

Also known as SIADH. 
It is caused by excessive anti-diuretic hormone (ADH, vasopressin) levels in the bloodsteam.

 

Causes

• Inappropriately excessive levels of ADH are released from the hypothalamus and posterior pituitary.
• ADH secretion from small cell lung cancer. This is an example of a paraneoplastic syndrome. 

 

See also

• Diabetes insipidus

Pituitary adenoma

Physiology

•   See: Pituitary gland and the hypothalamus 

 

Pathophysiology

• The neoplasm occupies space in the skull and may raise intracranial pressure. 
• The neoplasm may compress the optic chiasm, blocking signal propagation from the lateral retinal cells.

 

• Neoplasia of pituitary cells may cause hyperpituitarism (excessive pituitary activity). 
• Adenoma may produce excessive human growth hormone (hGH):  Pituitary gigantism (before closure of the growth plates). Acromegaly (after closure of the growth plates). 
• Adenoma may produce excessive prolactin: Unexpected lactation (in women or men).
• Adenoma may produce excessive cortisol: Hypercortisolism (Cushing's disease).

• Compression of normal pituitary cells may cause hypopituitarism (insufficient pituitary activity).
• Adenoma may disrupt human growth hormone (hGH) production: Pituitary dwarfism.
• Adenoma may disrupt prolactin production: Failure to lactate.
• Adenoma may disrupt production of follicle-stimulating hormone (FSH) and/or luteinizing hormone (LH): Infertility.
• Adenoma may disrupt cortisol production: Hypocortisolism (Addison's disease).  

 

Symptoms and signs

• Headache (various types, various mechanisms)
• Visual field defects, classically bitemporal hemianopia (optic chiasm compression)

• Hyperpituitarism
• Gigantism
• Acromegaly
• Unexpected lactation (in women or men) 

• Hypopituitarism
• (Proportional) dwarfism
• Oligo- or amenorrhoea 
• Infertility 
• Failure to lactate

Phaeochromocytoma

A phaeochromocytoma is a neoplasm of the adrenal medulla.

 

Pathophysiology

This produces excessive catecholamines, mostly norepinephrine and a significant amount of epinephrine.
The adrenergic signalling results in sympathetic nervous system hyperactivity. 

 

Symptoms and signs

• Secondary refractory hypertension
• Sinus tachycardia 
• Heart palpitations
• Chest pain 
• Anxiety
• Sweating 

Lambert–Eaton myasthenic syndrome

Disease class: Autoimmune diseases of the nervous system
Disease class: Nervous system paraneoplastic syndromes
Disease class: Neuromuscular junction diseases 

Also known as LEMS.

This is an example of a paraneoplastic syndrome.

 

Pathophysiology

1. A neoplasm over-expresses a voltage gated calcium channel (VGCC). Usually small cell lung cancer.
2. There is production of autoantibodies in response to this channel.
3. These autoantibodies bind to VGCCs in the pre-synaptic membranes at the neuromuscular junctions of skeletal muscles.
4. The blockade of the calcium channels prevents the influx of calcium ions.
5. This prevents the activation of the cellular machinery responsible for acetylcholine release. 
6. There is reduced acetylcholine signalling. 
7. There is a decrease in skeletal muscle contractility and autonomic function (e.g. gland secretions). 

There are other known mechanisms of autoantibody disruption of acetylcholine release in LEMS.

 

Symptoms and signs

• Proximal muscle weakness, which is usually relieved after exertion or exercise.
• The muscles of the legs and trunk are usually the worst affected.
• The muscles of the eyes are rarely affected.
• Dysfunction of the autonomic nervous system
• Dry mouth
• Constipation
• Blurred vision  

 

Investigations

• Nerve conduction study (NCS) 
• Electromyography (EMG)
• Voltage gated Ca2+ Antibodies

 

Management

• Medical therapy
• Treatment of underlying malignancy. 
• Acetylcholinesterase inhibitors
• Immunosuppression (therapeutic)
• Airway management
• Tracheal intubation
• Mechanical ventilation

 

Compare with 

• Botulism
• Guillain–Barré syndrome
• Myasthenia gravis
• Organophosphate poisoning

Transverse myelitis

Disease class: Demyelinating autoimmune diseases

Disease class: Myelitis 

Disease class: Nervous system paraneoplastic syndromes 

This is an inflammation of the myelin sheath in the spinal cord.

 

Symptoms

• Neuropathic pain 
• Sudden-onset
• Intense
• Weakness
• Paralysis
• Numbness
• Urinary incontinence

 

Investigations

• MRI spine: There may be visible lesions / plaques in the spinal cord.

Carcinoid syndrome

Carcinoid syndrome is a paraneoplastic syndrome. 

 

Pathophysiology

The syndrome is caused by the secretion of substances from a carcinoid tumour. The primary mediators are serotonin (a neurotransmitter) and kallikrein (an enzyme). Kallikrein catalyses conversion of kininogen to lysyl-bradykinin. This becomes bradykinin, a potent vasodilator.

There are elevated plasma histamine levels, but the mechanism through which this occurs is unclear. 

• Serotonin disturbs GI motility.
• Bradykinin causes facial vasodilation and flushing.
• Histamine causes bronchoconstriction.
• Serotonin promotes cardiac fibrosis, particularly at the tricuspid and pulmonary valves. 

 

Symptoms

• Facial flushing (due to vasodilation of superficial vessels in the skin)
• GI disturbances, especially diarrhoea, nausea, vomiting
• Abdominal pain, cramps
• Wheezing (due to narrowed bronchi)

 

Complications

• Carcinoid heart disease

 

Investigation findings

• Fibrosis of the valvular endocardium
• Secondary restrictive cardiomyopathy